Genome-wide analysis of histone modifications and gene expression during decidualization in human endometrial stromal cells.

• Project/Area Number: 25293343
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Yamaguchi University
• Principal Investigator: SUGINO Norihiro 山口大学, 医学(系)研究科(研究院), 教授 (10263782)
• Co-Investigator(Kenkyū-buntansha): YAMAGATA Yoshiaki 山口大学, 医学部附属病院, 准教授 (30363120)
• Co-Investigator(Renkei-kenkyūsha): SUYAMA Mikita 九州大学, 生体防御医学研究所, 教授 (70452365) ; OOKAWA Yasuyuki 九州大学, 医学研究院, 准教授 (80448430)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000); Fiscal Year 2015: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000); Fiscal Year 2014: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000); Fiscal Year 2013: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
• Keywords: 子宮内膜 / 脱落膜化 / エピジェネティクス / ヒストン修飾 / 転写調節 / 次世代シークエンサー

Outline of Final Research Achievements

Dramatic changes of gene expressions occur in human endometrial stromal cells (ESC) during decidualization. The changes in gene expression are associated with changes of chromatin structure, which are regulated by histone modifications. Here, we investigated genome-wide changes in histone modifications associated with decidualization in human ESC using next-generation sequencing. ESC were incubated with estradiol and medroxyprogesterone acetate to induce decidualization. Decidualization increased H3K27ac and H3K4me3 signals in many genomic regions. RNA-sequence showed that decidualization up-regulated 881 genes, 223 of which had H3K27ac- or H3K4me3-increased regions in the proximal and distal promoter regions. Pathway analysis revealed that up-regulated genes with the H3K27ac- or H3K4me3-increased regions were associated with the insulin signaling, which is involved in glucose uptake that is necessary for ESC to undergo decidualization.

Research Products

• [Journal Article] Changes in gene expression of histone modification enzymes in rat granulosa cells undergoing luteinization during ovulation. (2016)
  • Author(s): Maekawa R, Lee L, Okada M, Asada H, Shinagawa M, Tamura I, Sato S, Tamura H, Yamamoto S, Sugino N
  • Journal Title: Journal of Ovarian Research Volume: 9 Pages: 15-15
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Histone H3.5 forms an unstable nucleosome and accumulates around transcription start sites in human testis. (2016)
  • Author(s): Urahama T, Harada A, Maehara K, Horikoshi N, Sato K, Sato Y, Shiraishi K, Sugino N, Osakabe A, Tachiwana H, Kagawa W, Kimura H, Ohkawa Y, Kurumizaka H
  • Journal Title: Epigenetics & Chromatin Volume: 9 Pages: 2-2
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Tissue-specific expression of estrogen receptor 1 is regulated by DNA methylation in a T-DMR. (2016)
  • Author(s): Maekawa R, Sato S, Okada M, Lee L, Tamura I, Jozaki K, Kajimura T, Asada H, Yamagata Y, Tamura H, Yamamoto S, Sugino N
  • Journal Title: Molecular Endocrinology Volume: 30 Pages: 335-347
  • NAID: 130007024986
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Retinoic acid has the potential to suppress endometriosis development. (2015)
  • Author(s): Yamagata Y, Takaki E, Shinagawa M, Okada M, Jozaki K, Lee L, Sato S, Maekawa R, Taketani T, Asada H, Tamura H, Nakai A, Sugino N
  • Journal Title: Journal of Ovarian Research Volume: 8 Pages: 49-49
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Putative epimutagen in maternal peripheral and cord blood samples identified using human induced pluripotent stem cells. (2015)
  • Author(s): Arai Y, Hayakawaa K, Arai D, Ito R, Iwasaki Y, Saito K, Akutsu K, Takatori S, Ishii R, Hayashi R, Izumi S, Sugino N, Kondo F, Horie M, Nakazawa H, Makino T, Hirosawa M, Shiota K, Ohgane J
  • Journal Title: BioMed Research International Volume: 2015 Pages: 1-13
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Melatonin protects the integrity of granulosa cells by reducing oxidative stress in nuclei, mitochondria, and plasma membranes in mice. (2015)
  • Author(s): Tanabe M, Tamura H, Taketani T, Okada M, Lee L, Tamura I, Maekawa R, Aasada H, Yamagata Y, Sugino N
  • Journal Title: Journal of Reproduction and Development Volume: 61 Pages: 35-41
  • NAID: 130004703737
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Genome-wide analysis of histone modifications in human endometrial stromal cells. (2014)
  • Author(s): Tamura I, Ohkawa Y, Sato T, Suyama M, Jozaki K, Okada M, Lee L, Maekawa R, Asada H, Sato S, Yamagata Y, Tamura H, Sugino N
  • Journal Title: Molecular Endocrinology Volume: 28 Pages: 1656-1669
  • Peer Reviewed / Open Access
• [Journal Article] Genome-wide DNA methylation profiling in cultured eutopic and ectopic endometrial stromal cells. (2014)
  • Author(s): Yamagata Y, Nishino K, Takaki E, Sato S, Maekawa R, Nakai A, Sugino N
  • Journal Title: PLOS ONE Volume: 9（1）
  • Peer Reviewed / Open Access
• [Journal Article] Importance of C/EBPB binding and histone acetylation status in the promoter regions for induction of IGFBP-1, PRL and Mn-SOD by cAMP (2014)
  • Author(s): Tamura I, Sato S, Okada M, Tanabe M, Lee L, Maekawa R, Asada H, Yamagata Y, Tamura H, Sugino N
  • Journal Title: Endocrinology Volume: 155 Pages: 275-286
  • Peer Reviewed / Open Access
• [Journal Article] Molecular mechanism of luteinization. (2014)
  • Author(s): Sugino N
  • Journal Title: Obstetrics & Gynecology Science Volume: 57 Pages: 93-101
  • NAID: 110009586174
  • Peer Reviewed / Open Access
• [Journal Article] Potential mechanisms of aberrant DNA hypomethylation on the X chromosome in uterine leiomyomas. (2014)
  • Author(s): Sato S, Maekawa R, Yamagata Y, Asada H, Tamura I, Lee L, Okada M, Tamura H, Sugino N
  • Journal Title: Journal of Reproduction and Development Volume: 60 Pages: 47-54
  • NAID: 130003381861
  • Peer Reviewed / Open Access
• [Journal Article] Importance of C/EBPB binding and histone acetylation status in the promoter regions for induction of IGFBP-1, PRL and Mn-SOD by cAMP in human endometrial stromal cells. (2014)
  • Author(s): Tamura I, Sato S, Okada M, Tanabe M, Lee L, Maekawa R, Asada H, Yamagata Y, Tamura H, Sugino N
  • Journal Title: Endocrinology Volume: 155 Pages: 275-286
  • Peer Reviewed
• [Journal Article] Changes in histone modification and DNA methylation of the StAR and Cyp19a1 promoter regions in granulosa cells undergoing luteinization during ovulation in female rats. (2013)
  • Author(s): Lee L, Asada H, Kizuka F, Tamura I, Maekawa R, Taketani T, Sato S, Yamagata Y, Tamura H, Sugino N
  • Journal Title: Endocrinology Volume: 154 Pages: 458-470
  • Peer Reviewed
• [Presentation] 教育講演：黄体化の分子メカニズム (2016)
  • Author(s): 杉野 法広
  • Organizer: 第20回日本生殖内分泌学会
  • Place of Presentation: 神戸市,(神戸国際会議場)
  • Year and Date: 2016-01-09
  • Invited
• [Presentation] Tissue-specific expression of estrogen receptor 1 is regulated by DNA methylation in a T-DMR (tissue-dependent and differentially methylated region). (2015)
  • Author(s): Asada H, Okada M, Tamura H, Sugino N
  • Organizer: The 71th Annual meeting of the American Society of Reproductive Medicine 2015
  • Place of Presentation: Baltimore, USA
  • Year and Date: 2015-10-17
  • Int'l Joint Research
• [Presentation] 特別講演：子宮内膜脱落膜化とエピジェネティクス (2015)
  • Author(s): 杉野 法広
  • Organizer: 第132回近畿産科婦人科学会学術集会
  • Place of Presentation: 神戸市,(神戸国際会議場)
  • Year and Date: 2015-06-27
  • Invited
• [Presentation] Tissue-specific expression of estrogen receptor 1 is regulated by DNA methylation in a T-DMR (tissue-dependent and differentially methylated region). (2015)
  • Author(s): Maekawa R, Okada M, Tamura H, Sugino N.
  • Organizer: 48th Annual Meeting of the Society for the Study on Reproduction
  • Place of Presentation: Puerto Rico, USA
  • Year and Date: 2015-06-18
  • Int'l Joint Research
• [Presentation] シンポジウム：着床に伴う脱落膜化とその分子機構 (2015)
  • Author(s): 杉野法広
  • Organizer: 第60回日本生殖医学会
  • Place of Presentation: 横浜市,(パシフィコ横浜)
  • Year and Date: 2015-04-27
  • Invited
• [Presentation] Epigenome-transcriptome-interactome approach facilitates the investigation of undelying epigenetical deregulation in uterine leiomyomas. (2015)
  • Author(s): Maekawa R, Sato S, Jozaki K, Okada M, Shinagawa M, Lee L, Asada H, Taketani T, Yamagata Y, Tamura H, Sugino N.
  • Organizer: IFFS (International Federation of Fertility Society)/JSRM (Japan Society for Reproductive Medicine) International Meeting 2015
  • Place of Presentation: Yokohama, (パシフィコ横浜)
  • Year and Date: 2015-04-26
  • Int'l Joint Research
• [Presentation] Genome-wide analysis of histone modifications in human endometrial stromal cells undergoing decidualization by next-generation sequencing. (2015)
  • Author(s): Jozaki K, Okada M, Maekawa R, Tamura H, Sugino N.
  • Organizer: IFFS (International Federation of Fertility Society)/JSRM (Japan Society for Reproductive Medicine) International Meeting 2015
  • Place of Presentation: Yokohama, (パシフィコ横浜)
  • Year and Date: 2015-04-26
  • Int'l Joint Research
• [Presentation] 生涯研修プログラム：プロゲステロン産生調節 (2015)
  • Author(s): 杉野法広
  • Organizer: 日本産科婦人科学会学術集会
  • Place of Presentation: 横浜市,(パシフィコ横浜)
  • Year and Date: 2015-04-12
  • Invited
• [Presentation] 黄体機能の基礎知識－不妊治療への示唆－ (2014)
  • Author(s): 杉野法広
  • Organizer: 日本生殖医学会学術講演会
  • Place of Presentation: 東京都,新宿区（京王プラザホテル）
  • Year and Date: 2014-12-04 – 2014-12-05
  • Invited
• [Presentation] 子宮内膜の発育とその異常 (2014)
  • Author(s): 杉野法広
  • Organizer: 日本産婦人科医会学術集会
  • Place of Presentation: 香川県高松市,(JRホテルクレメント高松)
  • Year and Date: 2014-10-12
  • Invited
• [Presentation] Epigenome-interactome approach facilities the investigation of underlying epigenetical deregulation in uterine leiomyomas. (2014)
  • Author(s): R. Maekawa , I. Tamura , N. Sugino
  • Organizer: 47th Annual Meeting of the Society for the Study on Reproduction
  • Place of Presentation: Grand Rapids, USA
  • Year and Date: 2014-07-18 – 2014-07-23
• [Presentation] Genome-wide analysis of histone modifications associated with decidualization in human endometrial stromal cells. (2014)
  • Author(s): I. Tamura , R. Maekawa , N. Sugino
  • Organizer: 47th Annual Meeting of the Society for the Study on Reproduction
  • Place of Presentation: Grand Rapids, USA
  • Year and Date: 2014-07-18 – 2014-07-23
• [Presentation] Induction of IGFBP-1, PRL and Mn-SOD by cAMP is associated with histone acetylation status of their promoters in human endometrial stromal cells. (2014)
  • Author(s): H. Asada, M Okada, H. Tamura, N.Sugino
  • Organizer: The 30th Annual Meeting of the European Society of Human Reproduction and Embryology
  • Place of Presentation: Munich, Germany
  • Year and Date: 2014-06-28 – 2014-07-02
• [Presentation] Induction of IGFBP-1, PRL, and Mn-SOD by cAMP is associated with histone acetylation status of C/EBP b binding site of their promoters in human endometrial stromal cells. (2014)
  • Author(s): N. Sugino, I. Tamura
  • Organizer: 61st Annual meeting of Society for Gynecologic Investigation
  • Place of Presentation: Florence, Italy
• [Presentation] Induction of IGFBP-1 and PRL by cAM is associated with histone acetylation in the promoter region in human endometrial stromal cells. (2013)
  • Author(s): I. Tamura, N. Sugino
  • Organizer: Society for Reproductive Medicine
  • Place of Presentation: Boston, MA, USA
• [Presentation] Molecular mechamisms of luteinization.
  • Author(s): N. Sugino
  • Organizer: The 13th Korea-Japan Joint Conference of Obstetrics and Gynecology
  • Place of Presentation: Seoul, Korea
  • Invited